title: Prognostic utility of β-tubulin isotype III and correlations with other molecular and clinicopathological variables in patients with early breast cancer: a translational Hellenic Cooperative Oncology Group (HeCOG) study.
abstract: We evaluated the prognostic and predictive utility of β-tubulin isotype III (TUBB3) tumour gene transcription in early breast cancer patients enrolled in a randomised study. Quantitative reverse transcription-polymerase chain reaction (qRT-PCR) was applied for assessment of TUBB3, ER, PgR, HER2 and MAPT messenger RNA and immunohistochemistry (IHC) for protein expression in 314 patients enrolled in trial HE10/97, evaluating epirubicin-alkylator adjuvant chemotherapy with or without paclitaxel. High TUBB3 mRNA status was associated with advanced T stage, high histological grade, low mRNA and protein levels of ER, PgR and MAPT, and high levels of HER2 (p < 0.001). At a median follow-up of 98 months, multivariate analysis showed high TUBB3 mRNA status to have prognostic significance for DFS (HR = 1.83, 95% CI 1.25-2.68, p = 0.002) and OS (HR = 1.71, 95% CI 1.03-2.83, p = 0.038), along with the number of involved axillary nodes, PgR mRNA status and tumour grade. TUBB3 mRNA levels did not predict benefit from inclusion of paclitaxel in adjuvant chemotherapy (test for interaction p = 0.96 for OS, p = 0.46 for DFS). Transcriptional activity of β-tubulin isotype III in early breast cancer is an adverse prognostic factor, though not a predictive one for taxane efficacy.
authors.affiliation: Department of Medical Oncology, Ioannina University Hospital, Niarxou Avenue, 45500 Ioannina, Greece. gpenther@otenet.gr
authors.forename: George
authors.initials: G
authors.lastname: Pentheroudakis
authors.forename: Anna
authors.initials: A
authors.lastname: Batistatou
authors.forename: Konstantine T
authors.initials: KT
authors.lastname: Kalogeras
authors.forename: Ralf
authors.initials: R
authors.lastname: Kronenwett
authors.forename: Ralph M
authors.initials: RM
authors.lastname: Wirtz
authors.forename: Evangelos
authors.initials: E
authors.lastname: Bournakis
authors.forename: Anastasia G
authors.initials: AG
authors.lastname: Eleftheraki
authors.forename: Dimitrios
authors.initials: D
authors.lastname: Pectasides
authors.forename: Mattheos
authors.initials: M
authors.lastname: Bobos
authors.forename: Irini
authors.initials: I
authors.lastname: Papaspirou
authors.forename: Sevasti
authors.initials: S
authors.lastname: Kamina
authors.forename: Helen
authors.initials: H
authors.lastname: Gogas
authors.forename: Angelos K
authors.initials: AK
authors.lastname: Koutras
authors.forename: Nicholas
authors.initials: N
authors.lastname: Pavlidis
authors.forename: George
authors.initials: G
authors.lastname: Fountzilas
mesh_terms: D000328:Adult; D000368:Aged; D001943:Breast Neoplasms / Q000175:diagnosis* / Q000235:genetics / Q000401:mortality / Q000473:pathology*; D005260:Female; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008875:Middle Aged; D015999:Multivariate Analysis; D009367:Neoplasm Staging; D011237:Predictive Value of Tests; D011379:Prognosis; D012333:RNA, Messenger / Q000378:metabolism; D012189:Retrospective Studies; D016019:Survival Analysis; D014404:Tubulin / Q000235:genetics / Q000378:metabolism*; D055815:Young Adult
chemical_list: D012333:RNA, Messenger; C498585:TUBB3 protein, human; D014404:Tubulin